| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,,
* Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia;
Immunology and Virology Program, Centre for Opthalmology and Visual Science, The University of Western Australia, Crawley, Western Australia, Australia;
Centre for Experimental Immunology, Lions Eye Institute, Nedlands, Western Australia, Australia;
Cancer Biology Program, Division of Hematology-Oncology, Beth Israel-Deaconess Medical Center and Havard Medical School, Boston, MA 02215;
¶ Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia;
|| Department of Pathology, University of Western Australia, Crawley, Western Australia, Australia; and
# Division of Immunology and Genetics, John Curtain School of Medical Research, Australian National University, Canberra, Australia
Cytotoxic lymphocytes express a large family of granule serine proteases, including one member, granzyme (Grz)M, with a unique protease activity, restricted expression, and distinct gene locus. Although a number of Grzs, including GrzM, have been shown to mediate target cell apoptosis in the presence of perforin, the biological activity of Grz has been restricted to control of a number of viral pathogens, including two natural mouse pathogens, ectromelia, and murine CMV (MCMV). In this article, we describe the first reported gene targeting of GrzM in mice. GrzM-deficient mice display normal NK cell/T cell development and homeostasis and intact NK cell-mediated cytotoxicity of tumor targets as measured by membrane damage and DNA fragmentation. GrzM-deficient mice demonstrated increased susceptibility to MCMV infection typified by the presence of more viral inclusions and transiently higher viral burden in the visceral organs of GrzM-deficient mice compared with wild-type (WT) mice. The cytotoxicity of NK cells from MCMV-infected GrzM-deficient mice remained unchanged and, like WT control mice, GrzM-deficient mice eventually effectively cleared MCMV infection from the visceral organs. In contrast, GrzM-deficient mice were as resistant as WT control mice to mouse pox ectromelia infection, as well as challenge with a number of NK cell-sensitive tumors. These data confirm a role for GrzM in the host response to MCMV infection, but suggest that GrzM is not critical for NK cell-mediated cytotoxicity.
This article has been cited by other articles:
|
|
 |
|
  L. Wu, L. Wang, G. Hua, K. Liu, X. Yang, Y. Zhai, M. Bartlam, F. Sun, and Z. Fan Structural Basis for Proteolytic Specificity of the Human Apoptosis-Inducing Granzyme M J. Immunol., July 1, 2009; 183(1): 421 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Cullen, I. S. Afonina, R. Donadini, A. U. Luthi, J. P. Medema, P. I. Bird, and S. J. Martin Nucleophosmin Is Cleaved and Inactivated by the Cytotoxic Granule Protease Granzyme M during Natural Killer Cell-mediated Killing J. Biol. Chem., February 20, 2009; 284(8): 5137 - 5147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Bovenschen, P. J. A. de Koning, R. Quadir, R. Broekhuizen, J. M. A. Damen, C. J. Froelich, M. Slijper, and J. A. Kummer NK Cell Protease Granzyme M Targets {alpha}-Tubulin and Disorganizes the Microtubule Network J. Immunol., June 15, 2008; 180(12): 8184 - 8191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Fellows, S. Gil-Parrado, D. E. Jenne, and F. C. Kurschus Natural killer cell-derived human granzyme H induces an alternative, caspase-independent cell-death program Blood, July 15, 2007; 110(2): 544 - 552. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
